Gene-Deactivation Finding May Be Clue in Alzheimer's Puzzle

A novel approach to treating Alzheimer's disease (AD) is suggested by research headed by Rudolph Tanzi, Ph.D., a professor of neurology at Harvard Medical School, and reported in the journal Neuron. For a long time, the APOE-e4 gene variant remained the only known genetic risk factor for late-onset Alzheimer's. Then recently, genomewide association studies performed on thousands of individuals led to the identification of more genes implicated in AD, one of which is called CD33.

Now Tanzi and his colleagues have found, in brain tissue samples taken from deceased individuals who had AD, that higher levels of CD33 in microglia—immune cells that clean up debris in the brain—were associated with an increased number of beta-amyloid plaques, a hallmark of the illness. Thus it looked as if the gene prevented beta-amyloid clearance in the brain. Indeed, when the researchers deactivated the CD33 gene in mice, they found that the deactivation enhanced the ability of microglia to clear up beta-amyloid molecules.

"This is the first time that we have direct evidence of a gene, CD33, that directly controls beta-amyloid clearance by microglia," Tanzi said in a press statement. "Our findings raise the exciting possibility that the inability of microglia to degrade beta-amyloid in Alzheimer's disease could be reversed therapeutically by inhibition of CD33 activity."

To read more about strategies that might be able to avert AD, see Psychiatric News here and here. Information about diagnosis and treatment of AD can be found in American Psychiatric Publishing's Clinical Manual of Alzheimer's Disease and Other Dementias.

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